Protein Function

• A molecule bound reversibly by a protein is called a ligand.
• Oxygen is poorly soluble in aqueous solution, meaning...

  It cannot be carried to tissues in a sufficient quantity because of it simply dissolving in the blood on the way.
• Iron and Copper have the strongest tendency to bind oxygen.
• Iron is incorporated into a protein-bound prosthetic group called heme.
• Hemes organic ring structure is referred to as protoporphyrin.
• Heme is bound to a single atom in its ferrous (FE2+) state.
• What group helps prevent the conversion of heme iron? What state is it preventing?

  The nitrogen atoms help prevent the conversion to the ferric (Fe3+) state, because it has electron-donating character.
• The monomeric myoglobin facilitates oxygen diffusion in muscle tissue.
• The tetrameric hemoglobin is responsible for oxygen transport in the bloodstream.
• Myoglobin is made up of 8 a-helical segments connected by bends.
• Kd is the equilibrium constant for the release of ligand.
• The more tightly a protein binds to a ligand, the lower the concentration of ligand required for half of the binding sites to be occupied.
• When heme is bound to myoglobin, its affinity for oxygen is increased by the presence of distal his.
• Myoglobin has a hyperbolic binding curve for oxygen.
• Is hemoglobin or myoglobin better for oxygen transport? Why?

  Hemoglobin, because it has multiple subunits and oxygen binding sites.
• Hemoglobin contains 4 heme prosthetic groups.
• Adult hemoglobin contains two achains and two beta chains
• The heme-binding pocket is made up of E and F helices in each subunit.
• The hydrophobic effect plays a major role in stabilizing hemoglobins interfaces.
• Oxygen has a higher affinity for hemoglobin in the R state.
• Oxygen binding stabilizes the R state.
• If an experiment is absent of oxygen the T state is more stable.
• What happens when oxygen binds to hemoglobin subunits while in the T-State?

  There is a conformational change to the R-state.
• pO2 is low in tissues, and high in the lungs.
• Hemoglobin binds oxygen in the lungs and releases it in the tissues.
• Hemoglobin goes through a transition state where T-state (low affinity) is moved to a R-state (high affinity)
• Hemoglobin has a sigmoid binding curve
• An allosteric protein is one in which the binding of a ligand to one site affects the binding properties of another site on the same protein.
• Ligands bind more tightly to the R-State.
• Hemoglobin carries two end products of cellular respiration: H+ and CO2, from the tissues to the lungs and kidneys.
• The binding of H+ and CO2 is inversely related to the binding of oxygen.
• fetal hemoglobin has a higher affinity for oxygen than maternal hemoglobin.
• Carbamates form salt bridges that help stabilize the T-state and promote the release of oxygen.
• BPG reduces hemoglobins affinity for oxygen.
• Sickle Cell is from the replacement of glutamate with valine.